Liver Fibrosis in Heart Failure: Prevalence, Outcomes and Proteomic Pathway Analysis from the BIOSTAT-CHF Cohort

Liver Fibrosis in Heart Failure: Prevalence, Outcomes and Proteomic Pathway Analysis from the BIOSTAT-CHF Cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Liver Fibrosis in Heart Failure: Prevalence, Outcomes and Proteomic Pathway Analysis from the BIOSTAT-CHF Cohort Paul Brennan, Mark Kang, Wouter Ouwerkerk, Mya Win, Muhammad Hussain, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9337426/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Liver disease is highly prevalent in heart failure (HF) and is associated with worse outcomes, although the pathophysiological mechanisms remain poorly understood. In 3,017 HF patients from the index and validation cohorts of BIOSTAT-CHF, the prevalence of liver fibrosis was 552 (18.3%) as estimated by FIB-4 ≥2.67. Patients with liver fibrosis showed greater signs of systemic congestion, hepatomegaly, jugular venous distension, and elevated right heart pressures. Liver fibrosis significantly predicted mortality or HF re-hospitalisation, with "burnt-out" fibrosis (advanced fibrosis with minimal steatosis) carrying the highest risk (LiverRisk score ≥10 and Hepatic steatosis index <30: HR 7.86 [4.03–15.1]). Proteomic pathway analysis of 359 biomarkers identified αv integrin and TGFβ receptor II as central mediators of fibrogenesis, linking extracellular matrix remodelling, suppressed angiogenesis and inflammation. These findings position αv integrin as a therapeutic target amenable to selective inhibition in patients with concomitant HF and liver fibrosis. Health sciences/Cardiology/Cardiovascular biology Health sciences/Gastroenterology/Hepatology/Liver diseases Health sciences/Biomarkers/Prognostic markers Full Text Additional Declarations Yes there is potential Competing Interest. M.Z.K.T., W.O., M.L.W., M.S.H., A.P.M.L., A.M.C., I.R.M., J.F.D. and C.C.L. declare no competing interests. P.N.B. discloses consultancy fees from Novo Nordisk, Madrigal, Boehringer Ingelheim, and Resolution Therapeutics and educational honoraria from Takeda and Novo Nordisk outside of the submitted work. A.A.V. received consultancy fees and/or research support paid to his employer from Adrenomed, Anacardio, AstraZeneca, Bayer AG, BMS, Boehringer Ingelheim, Cardurion, Corteria, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, Rycarma and Salubris Bio. Supplementary Files BIOSTATLiverGraphicalAbstract.pdf Graphical Abstract Supplementarytablesandfigures.pdf Supplementary Tables 1 - 9; Supplementary Figure 1 - 8 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9337426","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":618801938,"identity":"7f35a0c1-c5b9-4cba-b197-45df86b57a24","order_by":0,"name":"Paul 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P.N.B. discloses consultancy fees from Novo Nordisk, Madrigal, Boehringer Ingelheim, and Resolution Therapeutics and educational honoraria from Takeda and Novo Nordisk outside of the submitted work. A.A.V. received consultancy fees and/or research support paid to his employer from Adrenomed, Anacardio, AstraZeneca, Bayer AG, BMS, Boehringer Ingelheim, Cardurion, Corteria, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, Rycarma and Salubris Bio.","formattedTitle":"Liver Fibrosis in Heart Failure: Prevalence, Outcomes and Proteomic Pathway Analysis from the BIOSTAT-CHF Cohort","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9337426/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9337426/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Liver disease is highly prevalent in heart failure (HF) and is associated with worse outcomes, although the pathophysiological mechanisms remain poorly understood. 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